After studying this chapter, the student should be able to:
Understand the basic optics of the eye, including the optics of common refractive errors.
Understand basic eyelid, orbit, and ocular anatomy, as well as some of the common ocular disorders associated with each tissue.
Understand the role of the primary care physician in the treatment and diagnosis of some of the more common ocular pathologies, as well as have a basic understanding of when an ophthalmology consult is recommended.
There are >35 million individuals throughout the world who are legally blind and an additional 240 million individuals who are classified as having low vision. In the United States alone, the prevalence of blindness and low vision in middle-aged adults and the elderly is approximately 1 and 3 million people, respectively. Although we often focus on the physical burden the visually impaired experience when trying to function in a world that relies heavily on visual cues, we often fail to consider the full emotional impact of vision loss. When asked, many individuals state that their top health-related fear is loss of vision, above loss of a limb, being diagnosed with cancer, or even death. As one might expect, individuals who experience significant vision loss are at a much greater risk of developing depression. Further, although it is understood that loss of vision will have tremendous impact on the life of a visually impaired individual, it is also important to appreciate the impact on the family members and friends who help with their routine care. In many countries, it is the cultural norm for a family member to assume a full-time caretaking role to assist a visually impaired relative. Depending on the age of the individual with vision loss and the chosen caretaker, 1 or possibly 2 people may be removed from the workforce. Thus, not only are there personal health implications, there are also broad economic impacts of vision loss as well.
OPTICS & REFRACTIVE ERRORS
The eye is a specialized neurosensory organ whose primary purpose is to gather and process light stimuli emerging from the visual field and convert it into an electric signal that can be modified and propagated along the visual pathway to neurons in the brain for higher order processing. The first critical step is to focus the incoming light onto the retinal photoreceptors. The eye has a refractive power of approximately +60 diopters; with two-thirds of the refractive power being generated by the cornea and one-third of the refractive power being generated by the natural lens. If the axial length is matched correctly to the refractive power of the eye, parallel beams of light from a distant object (greater than approximately 20 feet away) will be perfectly focused on the retinal plane, and a clear image should be perceived by the individual. When the refractive power and axial length are matched, the person is said to be emmetropic. A mismatch between the refractive power of the eye and the axial length results in refractive errors (Figure 37–1) and the perception of a blurred image. Myopia, or nearsightedness, is a case where the refractive power of the eye in relation to the axial length is too long and the light is focused in front of the retinal plane. Lenses or contacts that cause divergence of light (ie, negative power) are used to correct this problem. Hyperopia, or farsightedness, is the opposite. The refractive power of the eye in relation to the axial length is too low, and the light is focused behind the retinal plane. Lenses or contacts that cause light to converge (ie, positive power) are used to treat hyperopia. If the cornea or lens imparts dissimilar refractive powers along different axes, this is termed astigmatism. There will be 2 focal lines generated, typically 90 degrees from each other, at different distances along the visual axis. The location of those focal lines either in front of, behind, or straddling the retinal plane determines the type of astigmatism. Astigmatism is corrected using lenses or contacts that provide different powers in different axes. Although refractive errors can be temporarily corrected using glasses or contact lenses, patients often consider elective refractive surgery, such as laser-assisted in situ keratomileusis (LASIK) for more permanent correction of refractive errors.
Different refractive states of the eye. A. Emmetropia. Image plane from parallel rays of light are focused on retina. B. Myopia. Image plane focuses anterior to retina. C. Hyperopia. Image plane focuses posterior to retina. D. Astigmatism, myopic type. Images in horizontal and vertical planes focus anterior to retina. E. Astigmatism, hyperopic type. Images in horizontal and vertical planes focus posterior to retina. F. Astigmatism, mixed type. Images in horizontal and vertical planes focus on either side of retina. (Reproduced with permission from Hay WW Jr, Levin MJ, Deterding RR, et al: Current Diagnosis & Treatment: Pediatrics, 23rd ed. New York, NY: McGraw Hill; 2016.)
Amblyopia: Permanent visual impairment in an anatomically normal eye that is caused by an abnormal development of the visual pathway and vision processing centers during childhood.
Axial length: The distance from the front of the corneal surface to the retinal plane.
Blindness: The best corrected visual acuity of an individual’s better seeing eye is 20/200 or worse.
Low vision: The best corrected visual acuity of an individual’s better seeing eye is 20/40 or worse.
Strabismus: A misalignment of the eyes that causes an inability to fixate both eyes on a single focal point or object at the same time.
Visual acuity: The ability of an individual to distinguish between 2 points or identify a specific shape at a certain distance relative to a standard “normal” individual. Someone with 20/40 vision would need to stand at 20 feet in order to distinguish an object that someone with normal vision could distinguish at 40 feet.
Visual field: The complete area that a single eye can see when the eye is held in a fixed position. The visual field of an eye comprises the full central and peripheral vision.
In most instances, refractive errors are corrected so that objects at a distance are in focus. In order to focus on near objects, we need to increase the refractive power of the eye, a process called accommodation. To focus on a near object, the ciliary muscle contracts and reduces the tension on the zonules that hold the lens in place. When zonular tension is reduced, the lens assumes a more convex shape, thus increasing its refractive power. As we age, the lens naturally becomes less compliant and loses the ability to change shape. This loss of accommodative power and inability to focus on near objects as we age is termed presbyopia. Typically, it is not clinically significant until the mid-40s, at which time reading glasses or bifocal lenses are prescribed.
The bony orbit is made of 7 bones—the frontal, zygomatic, maxillary, sphenoid, ethmoid, palatine, and lacrimal bones. These create a pear-shaped cavity that contains the globe, a portion of the optic nerve, the extraocular muscles, blood vessels, nerves, and adipose tissue. With a 35- to 40-mm opening, the eye is relatively well protected, but there is still a risk for significant injury from small objects or blunt force trauma to the globe and orbit.
Orbital rim and wall fractures can occur with direct blows to the periorbital region. Although rim fractures often occur as a result of the direct impact, fractures to the orbital walls are often secondary to increased orbital pressure as a result of globe retropulsion and compression of the orbital tissues. The elevated tissue pressure is significant enough to fracture or “blow out” the orbital wall, with the medial orbit and floor being at greatest risk. In many cases, the wall fracture immediately self-reduces and heals with conservative management. It is recommended that patients avoid blowing their nose or performing Valsalva maneuvers to prevent air within the sinuses being forced into the orbit. In addition, oral antibiotics should be considered for medial and floor fractures to prevent sinus contents from seeding the orbital tissue and causing an infection. Because the wall fractures quickly self-reduce, the greatest concern is herniation and incarceration of orbital tissue into the fracture site. Herniated tissue is often seen on orbital computed tomography (CT), but ocular examination will also reveal restriction of eye movements (Figure 37–2). If the rectus muscle is incarcerated, the oculocardiac reflex may be stimulated, resulting in nausea, vomiting, and bradycardia. This would prompt an evaluation for surgical removal of incarcerated tissue and repair of the fracture. Otherwise, many fractures are self-limited and heal without complication.
The right inferior rectus muscle is entrapped within this patient’s orbital floor fracture, limiting upward gaze. (Reproduced with permission from Knoop KJ, Stack LB, Storrow AB, et al: The Atlas of Emergency Medicine, 4th ed. New York, NY: McGraw Hill; 2016. Photo contributor: Lawrence B. Stack, MD.)
Injuries to the Orbital Globe
If the orbital bones do not manage to protect the eye, the globe itself can be injured as a result of a direct impact as well. Smaller objects may cause lacerations of the conjunctiva, cornea (Figure 37–3), and sclera. In addition, direct impacts can also cause pressure to build rapidly inside the eye and result in a posterior rupture of sclera. The sclera is most vulnerable directly behind the extraocular muscle insertions where it is the thinnest; however, ruptures can occur at any location. Any trauma resulting in a full-thickness laceration or rupture of the eye is termed an open globe injury and requires emergent surgical intervention.
Trauma to the eye resulting in an open globe injury with extrusion of some of the iris through the corneal wound. Note the abnormal, teardrop pupil. There is conjunctival injection (superior, medial [left side], and inferior) and subconjunctival hemorrhage (temporal, right side) causing this red eye. (Reproduced with permission from Usatine RP, Smith MA, Mayeaux EJ, Chumley HS: The Color Atlas and Synopsis of Family Medicine, 3rd ed. New York, NY: McGraw Hill; 2019. Photo contributor: Paul D. Comeau.)
Even without a rupture of the scleral coat or cornea, blunt trauma can cause significant injuries to internal ocular structures and bleeding inside the eye. A hyphema can form when blood accumulates in the anterior chamber of the eye (Figure 37–4). This blood can clog the natural drainage system of the eye and result in secondary glaucoma. It is imperative to determine the sickle cell status in any patient with a hyphema because sickled red blood cells have a much higher probability of clogging the outflow pathway and causing problems. Further, carbonic anhydrase inhibitors should be avoided in sickle cell patients with hyphemas due to their potential for exacerbating the sickling of red blood cells.
This hyphema, consisting of red blood cells, has completely layered out in the anterior chamber. (Reproduced with permission from Knoop KJ, Stack LB, Storrow AB, et al: The Atlas of Emergency Medicine, 4th ed. New York, NY: McGraw Hill; 2016. Photo contributor: Brice Critser, CRA, The University of Iowa and EyeRounds.org.)
Orbital and ocular infections are not uncommon and require a thorough ocular examination and often radiologic imaging to provide an accurate diagnosis. Orbital infections are divided into 2 categories—preseptal and postseptal—based on their relationship to the orbital septum. The septum is a fibrous sheet that separates the orbit and eyelid and serves as a relative barrier to the spread of infection. Preseptal cellulitis often results from minor lid trauma or an abrasion. Due to the mechanism of injury, the most likely organism causing preseptal cellulitis is Staphylococcus aureus. Patients are often febrile and present with eyelid erythema and edema as well as discomfort. Preseptal cellulitis can often be managed with oral antibiotics; however, intravenous (IV) antibiotics may be necessary in patients who do not respond to oral medications. Orbital cellulitis involves an infection posterior to the orbital septum. Often, orbital cellulitis results from direct extension of a sinus infection through the bony wall into the orbital cavity. Presence of a subperiosteal abscess along the orbital wall must be ruled out with imaging. The most common organisms are S aureus, Streptococcus pneumoniae, and occasionally fungi. Patients are often febrile and present with decreased vision, proptosis, restricted eye movements, pain with eye movement, lid edema, erythema, and possibly a relative afferent pupillary defect.
Treatment for orbital cellulitis requires IV antibiotics. Depending on the age of the patient and suspected pathogen, drainage of the periosteal abscess may be required. Finally, endophthalmitis, an infection inside the globe, constitutes a significant threat to vision. Although there are multiple potential etiologies, immediate postoperative (Staphylococcus epidermidis, S aureus, Streptococcus species, and Pseudomonas), traumatic (Bacillus, S epidermidis, Streptococcus species, S aureus), and endogenous seeding (Candida) are the most common. Late postoperative endophthalmitis, >6 weeks after surgery, is often caused by Propionibacterium acnes. Prevention is key to avoiding postoperative endophthalmitis. Use of 5% betadine solution as part of the surgical site preparation has been proven to significantly decrease postoperative endophthalmitis rates. Patients often present with pain and decreased vision. Ocular examination reveals intraocular inflammation and potentially a hypopyon, layering of white blood cells in the anterior chamber (Figure 37–5). A vitreous or aqueous humor sample should be taken for cultures and sensitivities, and intravitreal antibiotics should be given. In addition, topical and systemic antibiotics should be added depending on the presentation. If vision is reduced to light perception or worse, removal of the vitreous via vitrectomy in addition to aggressive antibiotic treatment has been shown to be beneficial.
Hypopyon in a patient with Behçet disease, consisting of white blood cells layered out in the inferior portion of the anterior chamber. (Reproduced with permission from Riordan-Eva, P, Augsburger JJ: Vaughan & Asbury’s General Ophthalmology, 19th ed. New York, NY: McGraw Hill; 2018.)
Idiopathic orbital inflammation, or orbital pseudotumor, is inflammation of the orbital tissues of unknown etiology. Diagnosis is often challenging. Patients often present with afebrile lid edema and erythema, restricted eye movement, proptosis, orbital pain, diplopia, and changes in vision. CT scans of the orbit show enlargement of the extraocular muscles (orbital myositis) and their respective tendons, enhancement of the sclera, and often enlargement of the lacrimal gland. The differential diagnosis must include preseptal and orbital cellulitis as well as thyroid eye disease (Graves ophthalmopathy). Graves patients will present with relatively painless proptosis, diplopia, strabismus, restricted eye movement, and CT evidence of orbital myositis that spares the tendons. Antibiotics are ineffective in orbital pseudotumor; however, systemic steroids often cause a rapid improvement in symptoms. In patients nonresponsive to steroid treatment, systemic chemotherapy may be required.
The eyelids serve multiple purposes. In addition to protecting the globe, the eyelids also assist in spreading the natural tears over the surface of the cornea. Blinking creates a natural pumping action that propels tears medially along the lid margin to the punctum. Tears enter the canalicular system and are transported through the nasolacrimal sac and duct before entering the nose at the inferior turbinate. A functional tear drainage system is integral to maintaining good vision and comfort.
Similar to the globe, the eyelids are at risk for injury by both blunt and sharp objects. Laceration of the eyelid typically requires a layered closure with sutures, with special attention being paid to the horizontal realignment of the eyelid structures. The key is to recognize when the lid margin and/or the tear drainage system (ie, the canaliculus) have been violated. The upper and lower punctum should be cannulated to ensure they are patent and intact. Any canalicular involvement (Figure 37–6) requires intubation and temporary stenting of the tear drainage system during closure to prevent scaring, permanent closure, and development of excessive tearing known as epiphora.
This complex eyelid laceration shows the displaced inferior punctum (arrow). This laceration clearly violates the canalicular structures. (Reproduced with permission from Knoop KJ, Stack LB, Storrow AB, et al: The Atlas of Emergency Medicine, 4th ed. New York, NY: McGraw Hill; 2016. Photo contributor: Harold Lee, MD.)
Various pathologies involving the eyelid margins can cause significant issues. Inflammation of the eyelid margin, known as blepharitis, can have several causes. If the inflammation is toward the anterior surface, the most common culprits include Staphylococcus infections or a dandruff-type reaction known as seborrheic blepharitis. Inflammation of the posterior margin of the eyelid is often the result of Meibomian gland inflammation. Patients often report itching, burning, and a foreign body sensation. Inspection of the lid margin shows roughening, crusting, and scaling along the lid margin, clogged or capped Meibomian glands, and a foamy tear layer. Conservative treatment with baby shampoo lid scrubs (50% dilution with water) and topical antibiotics is often curative. Oral antibiotics and addition of steroids may be necessary in some cases.
Infection or obstruction of the glands within the eyelid can cause an acute, severe inflammatory response. Involvement of the glands of Zeiss and the Meibomian glands results in an external hordeolum and chalazion, respectively. Each presents with a focal, red, painful swelling at or just behind the lid margin. Often, capped glands can be seen at the lid margin. Chalazions (Figure 37–7), which are most often inflammatory and not infectious, are treated conservatively with warm compresses and baby shampoo lid scrubs. If conservative treatment is not successful, surgical incision and curettage are performed. A similar regimen is prescribed for an external hordeolum; however, because of a higher likelihood of infectious etiology, antibiotics are also prescribed. If a chalazion or hordeolum recurs in the same location, a biopsy should be done to rule out a sebaceous carcinoma.
Chalazion of right upper lid. (Reproduced with permission from Riordan-Eva, P, Augsburger JJ: Vaughan & Asbury’s General Ophthalmology, 19th ed. New York, NY: McGraw Hill; 2018.)
OCULAR COAT & ANTERIOR SEGMENT
The ocular coat consists of the cornea and sclera, the structures that maintain the outer shape of the eye. The anterior segment of the eye is composed of all of the structures anterior to the vitreous face, including the cornea, anterior chamber, drainage angle of the eye (trabecular meshwork and Schlemm’s canal), iris, ciliary body, and the lens.
Ocular Coat & Conjunctiva
The conjunctiva is a continuous layer of tissue composed of nonkeratinized stratified columnar epithelium that lines the back of the eyelids (palpebral conjunctiva), the fornix, and the surface of the globe (bulbar conjunctiva) before terminating at the limbus. The conjunctival goblet cells secrete mucin into the tear film, helping the fluid distribute evenly over the surface of the eye. Typically, the conjunctiva is relatively transparent, allowing the white sclera to be seen underneath.
“Red eye” is a common chief complaint among patients and carries an extensive differential diagnosis. One of the most common causes of redness and irritation is conjunctivitis. Viral conjunctivitis (ie, “pink eye”) is caused by the adenovirus (Figure 37–8) and produces discomfort, watery discharge, and photophobia. Often viral conjunctivitis begins unilaterally and then becomes bilateral due to autoinoculation of the fellow eye. Treatment is supportive, with cool compresses and artificial tears. Frequent hand washing with frequent changes of sheets and towels is advised. In addition, patients should be instructed to avoid touching their eyes to prevent spread. This can be contrasted with bacterial conjunctivitis, which is associated with more purulent discharge (Figure 37–9). Rapidly progressing conjunctivitis with copious discharge and preauricular lymphadenopathy is concerning for Neisseria gonorrhoeae infection. More moderate discharge and slower development could be caused by S pneumoniae, Staphylococcus species, Haemophilus influenzae, or Pseudomonas. All suspected bacterial conjunctivitis should be treated with topical antibiotics. Cultures can be obtained if empiric treatment is not working or the infection recurs.
Bilateral viral conjunctivitis in a 41-year-old man. (Reproduced with permission from Usatine RP, Smith MA, Mayeaux EJ, Chumley HS: The Color Atlas and Synopsis of Family Medicine, 3rd ed. New York, NY: McGraw Hill; 2019. Photo contributor: Richard P. Usatine, MD.)
Mucopurulent discharge, conjunctival injection, and lid edema are noted in a pediatric patient with bacterial (Haemophilus influenzae) conjunctivitis. (Reproduced with permission from Knoop KJ, Stack LB, Storrow AB, et al: The Atlas of Emergency Medicine, 4th ed. New York, NY: McGraw Hill; 2016. Photo contributor: Frank Birinyi, MD.)
Allergic conjunctivitis can be mistaken for viral conjunctivitis due to its similar appearance. Allergic conjunctivitis is a type I hypersensitivity reaction to various allergens. Patients present with conjunctival injection, conjunctival edema (chemosis), itching, and watery discharge. Many patients will admit to seasonal allergies and may have associated allergic rhinitis. Patients with a medical history of eczema or asthma are at risk for atopic keratoconjunctivitis, which is a combination of type I and IV hypersensitivity reactions. Atopic conjunctivitis can progress to cause foreshortening of the conjunctival fornix, symblepharon formation, and corneal scaring. Finally, patients can develop giant papillary conjunctivitis as a reaction to the presence of a chronic foreign body (eg, contact lenses or nondissolvable sutures postoperatively). Papillae are best seen by everting the lid and looking for a cobblestone appearance on the tarsal surface. Treatment for allergic conjunctivitis is supportive with cool compresses and artificial tears, which help dilute the allergen burden. In addition, use of topical and systemic antihistamines and topical mast cell stabilizers can be beneficial. Topical nonsteroidal anti-inflammatory drugs and steroids can be used sparingly for refractory cases.
Subconjunctival hemorrhages can be striking in their appearance (Figure 37–10) but are usually benign. The hemorrhage arises from blood vessels either within the conjunctiva or the sclera that bleed into the space between the 2 tissues. Often no etiology can be found; however, eye rubbing and Valsalva from coughing or emesis are common. Trauma can lead to subconjunctival hemorrhage as well. Depending on other ophthalmic exam findings, the presence of 360 degrees of subconjunctival hemorrhage around the cornea after ocular trauma warrants strong consideration for surgical exploration to rule out a ruptured globe.
A 360-degree subconjunctival hemorrhage is seen in this patient after blunt trauma to the eye and orbit. Note that the hemorrhage stops abruptly at the limbus. (Reproduced with permission from Knoop KJ, Stack LB, Storrow AB, et al: The Atlas of Emergency Medicine, 4th ed. New York, NY: McGraw Hill; 2016. Photo contributor: Brice Critser, CRA, The University of Iowa and EyeRounds.org.)
Pinguecula and pterygium are relatively benign growths that are commonly seen on the conjunctiva. A pinguecula is a small whitish-yellow spot located near the corneal limbus. It appears nasally more often than temporally and represents an accumulation of protein, calcium, or fat in the conjunctiva. Pingueculae are completely benign. A pterygium is a triangular or wing-shaped growth that extends from the perilimbal conjunctiva onto the cornea (Figure 37–11). It is thought to be exacerbated by long-duration exposure to arid climates, ultraviolet light, and wind (thus its nicknames of “farmer’s eye” and “surfer’s eye”). As the growth progresses, it can induce significant astigmatism and encroach on the visual axis. If vision becomes affected, surgical excision is warranted; however, pterygia often recur.
This fibrovascular pterygium has grown onto the cornea but has not yet obscured the visual axis. The pterygium has the shape of a bird’s wing, the literal definition of “pterygium.” (Reproduced with permission from Usatine RP, Smith MA, Mayeaux EJ, Chumley HS: The Color Atlas and Synopsis of Family Medicine, 3rd ed. New York, NY: McGraw Hill; 2019. Photo contributor: Richard P. Usatine, MD.)
Maintaining adequate hydration of the ocular surface is critical for good vision and comfort. Dry eyes, known as keratoconjunctivitis sicca, is a relatively common finding. Patients complain of a foreign body sensation, burning, or dryness, which is often worse late in the day or when doing activities that require visual concentration such as driving, watching television, reading, or working on the computer. Several clinical tests are useful in diagnosing dry eyes. Tear breakup times of <10 seconds are considered abnormal. Schirmer testing involves placement of a filter paper strip inside the temporal lower eyelid. Less than 10 mm of wetting after 5 minutes is considered abnormal. On examination at the slit lamp, a decreased tear lake can be seen. In addition, dryness can cause small punctate epithelial erosions that expose the underlying basement membrane. Fluorescein dye stains the basement membrane yellow under a cobalt blue light; thus, a yellow speckled pattern is indicative of dry eyes. Rose bengal and lissamine green can be used to stain devitalized corneal cells as well. Treatment starts with topical application of artificial tears and/or ointments for hydration. If this is insufficient, topical cyclosporine can be prescribed to increase tear production. For more severe cases, punctal occlusion may be necessary and serum autologous tears can be tried. Often patients find the use of a humidifier in the house helpful as well.
The cornea is approximately 12 mm in diameter and has a central and peripheral thickness of approximately 540 µm and 1 mm, respectively. The cornea is composed of 5 layers that can be remembered by the mnemonic ABCDE: anterior epithelium, Bowman membrane, corneal stroma, Descemet membrane, and endothelium. The highly organized arrangement of the stromal collagen fibrils, glycosaminoglycans, and other components is critical to maintaining corneal transparency. In addition, the cornea is densely innervated; thus, it is highly sensitive.
Corneal abrasions are relatively common and can be caused by a variety of objects, with fingernails, tree branches or foliage, and makeup applicators being common culprits. Often patients present with severe pain, tearing, conjunctival injection, and photophobia. Application of a drop of topical anesthetic often brings immediate relief of symptoms. Ocular examination should include placing a drop of fluorescein in the eye and examining under magnification. A slit lamp is preferable; however, the cobalt light of the direct ophthalmoscope and a magnifying lens can be used. Again, the abrasion will appear bright yellow as the epithelial disruption allows the fluorescein to stain the underlying basement membrane (Figure 37–12). In addition, there may be cells observed in the anterior chamber. The lids should be everted to examine for foreign bodies trapped in the fornix or on the palpebral conjunctiva behind the tarsus. Most foreign bodies can be removed with a cotton-tipped applicator. A corneal foreign body requires specialized attention, and removal should be done by an ophthalmologist at the slit lamp or in the operating room if there is concern for full-thickness penetration of the cornea. Topical antibiotics should be administered, with a fourth-generation fluoroquinolone used for any abrasions caused by vegetable matter or in contact lens wearers to prevent Pseudomonas infection. A bandage contact lens or patching overnight may be used in cases of extreme discomfort but only if reexamination the following day is possible. Cycloplegia can reduce photophobia caused by ciliary muscle spasm. Steroids are contraindicated because they will slow the healing of the epithelium. Finally, numbing drops such as proparacaine are never prescribed for a patient because repeated use is toxic to the epithelium and will worsen the condition.
Corneal abrasion. A. This corneal abrasion obscures the visual axis and will benefit from close follow-up with an ophthalmologist to ensure adequate healing. B. Eversion of the upper eyelid reveals a retained foreign body. Without removal, this would likely continue to abrade the cornea with each blink or eye movement. (Reproduced with permission from Knoop KJ, Stack LB, Storrow AB, et al: The Atlas of Emergency Medicine, 4th ed. New York, NY: McGraw Hill; 2016. Photo contributor: Lawrence B. Stack, MD.)
Corneal ulcerations can have a devastating impact on visual acuity when the ulcer or residual scar is located in the visual axis (Figure 37–13). A complete discussion on the types of noninfectious corneal ulcers and their pathogenesis is beyond the scope of this chapter; however, a basic understanding of infectious keratitis is important. Patients typically present with a history of corneal trauma or contact lens wear, but severe keratoconjunctivitis sicca or eyelid abnormalities can predispose to infections as well. Staphylococcus, Streptococcus, Pseudomonas, and Moraxella species are some of the most common culprits after the epithelium has been disrupted. However, there are some bacteria, such as N gonorrhoeae and Corynebacterium diphtheriae, that can penetrate an intact epithelium and cause ulceration. Patients often have redness, photophobia, watering or discharge, and decreased visual acuity if the central axis is involved. Ocular examination should include staining with fluorescein to determine whether an epithelial defect is present and look for corneal opacification. The baseline size and shape of both the epithelial defect and infiltrate should be recorded, along with the degree of corneal thinning. Presence or absence of an anterior chamber reaction and hypopyon should also be noted. Corneal scrapings are obtained and sent for cultures and staining (Gram +/– Giemsa stain). Patients are typically treated empirically with fortified antibiotics if the ulcer is >1 mm. Initially, vancomycin (or cefazolin) and tobramycin are alternated every 30 minutes to 1 hour and then tapered as improvement is noted. If the patient is a contact lens wearer, the contacts should be cultured and discarded. New contacts should not be worn until the infection is completely resolved. Further, contact lens wearers who sleep in their contacts should be educated on the dangers associated with that practice. Steroids can help minimize permanent scaring and opacification, but they should not be started until there is definitive evidence of improvement (typically after about 48 hours). For ulcers refractory to antibiotic therapy, one must consider a fungal or protozoan (Acanthamoeba) species.
Diffuse conjunctival injection and cloudy cornea demonstrating keratitis with corneal ulcer formation and a leucocyte infiltrate. (Reproduced with permission from Usatine RP, Smith MA, Mayeaux EJ, Chumley HS: The Color Atlas and Synopsis of Family Medicine, 3rd ed. New York, NY: McGraw Hill; 2019. Photo contributor: Paul D. Comeau.)
Although bacterial keratitis can have devastating impacts on vision, herpetic keratitis is actually the leading cause of infectious corneal blindness, with herpes simplex virus (HSV) type 1 infection being more common than HSV type 2. The classic dendritic staining pattern after application of fluorescein is pathognomonic for HSV keratitis (Figure 37–14); unfortunately, this presentation is not common. Often patients present with unilateral vesicular blepharitis or follicular conjunctivitis that can be confused with other forms of conjunctivitis. Epithelial keratitis is also common with stromal infiltration, but conjunctivitis may be absent in these cases. HSV keratitis is often recurrent as a result of virus reactivation and must be monitored closely. Treatment often is based on presentation but typically involves the use of topical antivirals (ganciclovir). Use of steroids has been shown to be beneficial for stromal involvement but should be monitored closely due to the potential adverse effects (eg, glaucoma, secondary bacterial keratitis, corneal perforation). Oral acyclovir has been shown to reduce the rate of recurrence, so patients are often treated for at least 1 year prior to attempting to taper the oral medications.
This close-up view of an eye with herpetic keratitis shows the branching pattern of a viral dendrite after installation of fluorescein stain and illumination with a cobalt blue light. (Reproduced with permission from Riordan-Eva P, Augsburger JJ: Vaughan & Asbury’s General Ophthalmology, 19th ed. New York, NY: McGraw Hill; 2018.)
Herpes zoster infection of the eye, herpes zoster ophthalmicus (HZO), is due to the reactivation of the varicella virus within the trigeminal nerve. Although reactivation in the ophthalmic branch (V1) is the most likely to cause of ocular involvement, reactivation in the maxillary (V2) and mandibular (V3) branches can also lead to HZO. Presence of the Hutchinson sign (Figure 37–15), defined as vesicular lesions on the side or tip of the nose, makes ocular involvement more likely. The HZO vesicular rash respects the midline. Treatment involves use of acyclovir, if it can be started within 48 to 72 hours of the first vesicle appearance. In addition, oral steroids can also be used and have been shown to reduce the duration of the disease. Topical antibiotics may be applied to the eye for secondary infections and cycloplegia for photophobia. In addition to ocular involvement, postherpetic neuralgia is a major concern and may require consultation with a neurologist or pain specialist. For this reason, the varicella vaccine should be given to the elderly in order to help prevent HZO.
This classic herpes zoster ophthalmicus vesicular rash is in the ophthalmic division (V1) of the trigeminal nerve. The presence of the lesion near the tip of the nose (Hutchinson sign) increases the risk of ocular involvement. (Reproduced with permission from Knoop KJ, Stack LB, Storrow AB, et al: The Atlas of Emergency Medicine, 4th ed. New York, NY: McGraw Hill; 2016. Photo contributor: Lawrence B. Stack, MD.)
Finally, chemical burns to the eye require immediate attention. If patients contact the physician by phone prior to presenting to the clinic or emergency department, they should be instructed to wash the eye out for several minutes before traveling to the physician with any clean source of water immediately available. In addition, the patient should be instructed to bring in the label or a picture of the offending agent if possible. Acids will denature and precipitate corneal proteins, which can create a protective barrier that prevents deeper penetration. Alkali chemicals, on the other hand, will only denature the proteins and saponify fat. The lack of protein precipitation allows for deeper penetration (Figure 37–16). Thus, alkali burns are often considered more worrisome. Treatment involves placing a drop of topical anesthetic into the eye, testing the pH (normal 7.4), and then using copious irrigation with lactated Ringer’s or saline until the pH normalizes. A Morgan lens is helpful. If trouble normalizing the pH is noted, a cotton-tipped applicator or glass rod can be used to clear the fornix of any residual solid chemical that may be trapped. After the pH is normalized, the patient should be given topical antibiotics and cycloplegics. Addition of steroids, antiglaucoma medications, ascorbate and/or citrate, and collagenase inhibitors may be necessary depending on the severity of the burn. It is important to watch for cicatricial conjunctival changes and break any adhesions that begin to form during the healing process. Many patients will eventually need corneal transplants; however, success rates are highly variable depending on the severity of the chemical burn.
Diffuse opacification of the cornea occurred from a “lye” (alkali) burn to the face. (Reproduced with permission from Knoop KJ, Stack LB, Storrow AB, et al: The Atlas of Emergency Medicine, 4th ed. New York, NY: McGraw Hill; 2016. Photo contributor: Stephen W. Corbett, MD.)
The lens of the eye is typically transparent and works in concert with the cornea to focus light on the retina. The lens has essentially 3 layers: a central nucleus, a surrounding cortex, and an outer lens capsule. An opacification in any layer of the lens is called a cataract, and it can be detected on examination by a reduction of the red reflex with direct ophthalmoscopy or direct observation at the slit lamp. Regardless of the etiology or location, the common end result of a cataract is light being scattered instead of focused on the retina. This results in the perception of a degraded image and decreased visual acuity. Cataract removal is an outpatient procedure and is the most common surgery performed in the United States. Cataract development is a natural process that is often first noted on examination around the age of 50 years. However, the rate of progression and degree of visual dysfunction is highly variable. The only method to treat cataracts is surgical removal of the natural crystalline lens while attempting to spare the lens capsule. A new artificial lens is then placed inside the capsular bag for support. Cataract surgery is only recommended when the cataract has become visually significant, which typically means best corrected visual acuity of 20/40 or worse and a functional complaint. Common functional complaints include the inability to drive at night due to headlight glare, the inability to read, and the inability to see the television or computer clearly. Although cataract development is typically a natural process of aging, formation can be caused or accelerated by various diseases and medications, including ocular trauma, diabetes, uveitis, steroid use, radiation exposure, atopic dermatitis, Down syndrome, myotonic dystrophy, neurofibromatosis type 2, retinitis pigmentosa, Werner syndrome, and Wilson disease, among others. Special consideration is given to congenital cataracts, which are present at birth. It is imperative that primary care physicians check for cataracts in all children by observing the red reflex, because missing the diagnosis can result in permanent vision loss (amblyopia; see section later in this chapter on amblyopia).
The lens is typically centered along the visual axis in line with the pupil. It is held into position by zonular fibers that connect from the lens capsule near the equator to the ciliary body located behind the iris 360 degrees. Zonular disruption can result in subluxation or dislocation of the lens, known as ectopia lentis. The most common causes are ocular trauma (Figure 37–17), Marfan syndrome (typically superior subluxation), homocystinuria (typically inferior subluxation), aniridia, Weill-Marchesani syndrome, microspherophakia, and syphilis, among others.
The crescentic edge of this dislocated crystalline lens is visible within the pupil and creates an abnormal red reflex. (Reproduced with permission from Knoop KJ, Stack LB, Storrow AB, et al: The Atlas of Emergency Medicine, 4th ed. New York, NY: McGraw Hill; 2016. Photo contributor: Thomas Egnatz, CRA.)
The iris is a flat, round structure attached to the sclera and ciliary body near the corneoscleral junction. The iris has a central opening, the pupil, which can be dilated or constricted by activation of the dilator pupillae or sphincter muscles, respectively. The ability to regulate the size of the pupil is critical for allowing us to obtain good vision in a variety of light intensities. Eye color is determined by the amount of pigment contained in the iris, with lighter colored eyes (blue and green) having less pigment than darker (brown) eyes. The iris can obtain pathology related to systemic diseases. An excellent example of this is neurofibromatosis type 1, which is caused by a mutation in the neurofibromin 1 (NF1) gene located on chromosome 17. Neurofibromatosis type 1 results in multiple nervous system tumors throughout the body. In addition to skin neurofibromas, café-au-lait spots, and plexiform neurofibromas, patients will often have evidence of Lisch nodules (Figure 37–18) on the iris. These are iris hamartomas composed of dendritic melanocytes and appear as raised pigmented spots on the surface of the iris. They do not affect vision and are considered benign.
Lisch nodules (melanotic hamartomas of the iris) are clear yellow-to-brown, dome-shaped elevations that project from the surface of this blue iris. These hamartomas are the most common type of ocular involvement in neurofibromatosis type 1 and do not affect vision. (Reproduced with permission from Usatine RP, Smith MA, Mayeaux EJ, Chumley HS: The Color Atlas and Synopsis of Family Medicine, 3rd ed. New York, NY: McGraw Hill; 2019. Photo contributor: Paul D. Comeau.)
The uvea, Latin for “grape,” or uveal tract is composed of the iris, ciliary body, and choroid. These 3 structures compose a heavily pigmented, central layer in the eye and are occasionally susceptible to inflammation called uveitis. When the inflammation is isolated to the structures in front of the lens (ie, the iris and ciliary body), we often call this anterior uveitis or iridocyclitis. Patients often present with a complaint of decreased vision, pain, redness, and photophobia. Examination at the slit lamp is critical for diagnosis. The redness is often caused by ciliary flush, or dilation of the vessels close to the corneoscleral junction. The conjunctiva and outer layer of the sclera (episclera) may also be involved. The key aspect of the examination is observation of white blood cells floating in the anterior chamber or precipitation of those cells on the iris (iris nodules) or the cornea (keratic precipitates). Because of the natural convection current and aqueous movement in the eye, keratic precipitates are most often found in the inferior quadrant, known as the Arlt triangle (Figure 37–19). The majority of uveitis cases are idiopathic. Because a laboratory workup is only successful in approximately half of the cases, the first occurrence is often treated empirically, and only those individuals with recurrences have laboratory work completed. The full list of known causes of anterior uveitis is extensive, but some of the most common causes include human leukocyte antigen B27–associated uveitis (ankylosing spondylitis, Reiter syndrome/reactive arthritis, psoriatic arthritis, and inflammatory bowel disease), sarcoid, syphilis, tuberculosis, Behçet disease, juvenile rheumatoid arthritis, Fuchs heterochromic iridocyclitis, Lyme disease, herpetic infections, trauma, and others. Posterior uveitis is associated with inflammation of structures posterior to the lens, including vitreous cell or fibrin, inflammation of the retinal layer (vasculitis, exudation, retinitis, and retinal pigmented epithelial changes), and/or choroidal involvement (choroiditis or choroidal detachment). Again, the differential diagnosis for posterior uveitis is extensive, but some of the more common causes are toxoplasmosis, retinal vasculitis, sarcoid, tuberculosis, syphilis, Behçet disease, Vogt-Koyanagi-Harada disease, presumed ocular histoplasmosis, Eales disease, Lyme disease, amyloidosis, various forms of choroiditis (eg, birdshot, multifocal choroiditis, toxocariasis), various forms of retinitis (eg, cytomegalovirus, cysticercosis, onchocerciasis, acute retinal necrosis, candidiasis, Bartonella henselae [cat scratch disease]), and multiple sclerosis.
These granulomatous keratic precipitates are located on the inferior corneal endothelium (Arlt triangle) in a patient with uveitis. (Reproduced with permission from Riordan-Eva, P, Augsburger JJ: Vaughan & Asbury’s General Ophthalmology, 19th ed. New York, NY: McGraw Hill; 2018.)
Treatment for known causes of uveitis, such as infectious agents, is guided by the pathogen. In addition, the goal of all uveitis treatment is to reduce the inflammation. This is typically accomplished through the liberal use of steroids in the form of topical drops, periocular injections, intraocular injections, oral steroids, or implantation of a steroid-eluting pellet into the vitreous cavity. There is always a concern for secondary, steroid-induced glaucoma, so the intraocular pressure should be checked regularly. If steroids alone do not control the inflammation, systemic immune suppressants may be needed. In addition, in the setting of an acute episode, cycloplegics are often prescribed to reduce pain and avoid the development of a small fixed pupil as a result of adhesions between the pupillary margin and the lens capsule, known as posterior synechiae.
The posterior segment is made up of the structures located behind the lens of the eye. These include the vitreous, retina, choroid, and optic nerve.
The vitreous is a transparent gel. It is made up of 98% to 99% water, whereas the remaining 1% to 2% is an extracellular matrix consisting of fibrillar proteins (primarily collagen) and glycosaminoglycans (primarily hyaluronan), among other substances. The vitreous is most strongly attached to the retina at the optic nerve, blood vessels, and the ora serrata, which is the anterior termination of the retina. Although the vitreous typically remains clear, opacification of the vitreous can cause patients to notice a change in their vision. As a natural part of aging, the vitreous will go through a process of liquefaction and condensation. Usually around the age of 60 years, the vitreous will begin to pull away from its retinal and posterior pole attachments. Traction on the retina during this process can result in a perception of “flashes of light” known as photopsias. If small condensations of vitreous remain suspended just above the sensory retina after vitreal detachment, they can cast small shadows onto the retina that are perceived as “floaters.” Although a posterior vitreal detachment or vitreous degeneration is typically benign, the process of separating the vitreoretinal interface can cause breaks in the retinal vessels or a hole to be torn in the retina. Vitreous hemorrhage, regardless of the cause (eg, vitreous degeneration, hypertension, diabetes), can obscure the vision. Often the blood will layer out inferiorly until it is reabsorbed as long as the patient keeps his or her head upright and stable.
The neurosensory retina typically lines the inner wall of the eye between the vitreous and the choroid. The retinal layers from the innermost to outermost include the following: (1) retinal nerve fiber layer composed of ganglion cell axons; (2) ganglion cell layer composed of ganglion cell nuclei; (3) inner plexiform layer composed of bipolar and amacrine cell axons plus ganglion cell dendrites; (4) inner nuclear layer composed of horizontal, bipolar, and amacrine cell nuclei; (5) outer plexiform layer composed of photoreceptor axons plus horizontal and bipolar cell dendrites; (6) outer nuclear layer composed of photoreceptor cell bodies; (7) photoreceptor layer composed of inner and outer segments of the photoreceptors; and (8) retinal pigmented epithelium (RPE). Thus, light must travel through nearly all of the retinal layers prior to activating photoreceptor opsin pigments that initiate the process of turning light into an electrical signal, a process known as phototransduction.
There are several pathologies of the retina that can have a dramatic effect on vision. Occasionally, the retina will become detached. The most common cause of retinal detachment is the development of a hole or tear in the retina. Holes and tears can be caused by a variety of conditions, including vitreous degeneration and traction on the retina, as mentioned previously; trauma; lattice degeneration (thin peripheral retina); high myopia; and previous ocular surgery. Once a hole or tear develops, aqueous fluid or liquefied vitreous can enter the hole and propagate a detachment of the RPE from the photoreceptor layer (Figure 37–20). The detached retina will result in loss of vision from the corresponding visual field that is typically focused on that portion of the retina. If the retina remains intact over the macula and fovea, visual acuity is usually spared. If the fovea is involved, visual acuity will be significantly decreased. Therefore, patients experiencing flashes of light, new floaters, or the feeling like a curtain is coming over their vision should be instructed to see an eye care specialist for evaluation immediately. Evaluation requires a dilated examination with indirect ophthalmoscopy including scleral depression to examine the peripheral retina, where breaks mainly occur. If a clear view cannot be obtained by direct examination, an ultrasound of the eye can be completed. A detached retina will show up as a hyperechoic membrane within the vitreous space. Treatment of retinal detachment often includes a core vitrectomy, removal of subretinal fluid, laser cerclage around the hole, and introduction of gas into the eye to press the retina into position. Additional laser treatment may be used to help secure the retina to the wall of the eye. Postoperatively, the patient is often positioned face down, allowing the gas to retain pressure on the retina.
An illustration of liquid vitreous passing through a horseshoe retinal tear causing a retinal detachment. (Reproduced with permission from Riordan-Eva, P, Augsburger JJ: Vaughan & Asbury’s General Ophthalmology, 19th ed. New York, NY: McGraw Hill; 2018.)
The retina and choroid are highly vascularized structures and are susceptible to a variety of vascular pathologies. Diabetic retinopathy is a leading cause of blindness in the United States. It is estimated that >80% to 98% of patients with type 1 diabetes and approximately 60% to 90% of patients with type 2 diabetes will develop at least some diabetic retinopathy within 20 years of diagnosis. Early diabetic retinopathy is characterized by the selective loss of pericytes adjacent to capillary endothelial cells and microaneurysm formation. In addition, hard (white) exudates, cotton-wool spots (retinal nerve fiber layer infarcts), and venous beading can be seen (Figure 37–21). As the disease progresses, capillaries continue to close and drop out, creating larger areas of ischemia. With development of ischemia, multiple proangiogenic factors are made by the retina, and eventually new blood vessels begin to grow on the optic disk and retina. Thus, we separate diabetic retinopathy into nonproliferative diabetic retinopathy and the more advanced proliferative diabetic retinopathy based on the presence of new blood vessel growth. Vision loss caused by diabetic retinopathy is typically related to the development of macular edema in nonproliferative diabetic retinopathy and tractional retinal detachment and vitreous hemorrhage in proliferative disease. In addition, new blood vessels can also develop on the iris and in the drainage angle of the eye, resulting in neovascular glaucoma. Patients with diabetes should be seen 12 months after their initial diagnosis of diabetes and should be seen at least every year after that for a dilated funduscopic examination. Treatment for diabetic retinopathy involves developing and maintaining control of the patient’s blood sugars. In addition, focal laser and injection of anti–vascular endothelial growth factor (VEGF) medications can be used to control retinal edema. Proliferative disease often requires the use of panretinal photocoagulation, in which laser spots are placed in the peripheral retina in an attempt to ablate the unhealthy retina that is creating proangiogenic factors signaling neovascularization. The trade-off is development of scotomas at the sites where laser is applied.
Moderate nonproliferative diabetic retinopathy with multiple microaneurysms and hemorrhages, mild macular hard exudates, and 2 cotton-wool spots in the superior retina. (Reproduced with permission from Riordan-Eva, P, Augsburger JJ: Vaughan & Asbury’s General Ophthalmology, 19th ed. New York, NY: McGraw Hill; 2018.)
Although hypertensive retinopathy is known to worsen diabetic retinopathy, hypertension can cause significant retinal pathology and vision loss itself. Hypertension can cause vasoconstriction of retinal arterioles as well as breakdown of the blood–retina barrier. Patients will present with arteriovenous nicking, copper or silver wiring of the arteries, microaneurysms, hemorrhages, exudates, and cotton-wool spots. In addition, the optic nerve can also show pathology with disk edema and flame hemorrhages. Macular exudates may also be present (Figure 37–22). Patients may experience retinal ischemia and vision loss. Thus, any patient presenting with these signs and symptoms should have their blood pressure taken immediately while still in the office. Treatment is focused on the controlled lowering and maintenance of blood pressure because patients are at higher risk of multiple vision-threatening conditions (eg, retinal vein occlusion, ischemic optic neuropathies, worsening diabetic retinopathy) and life-threatening conditions (eg, stroke, heart attack, aneurysm).
Malignant hypertensive retinopathy with optic nerve head edema (papilledema), flame hemorrhages (white arrow), cotton-wool spots (black arrow), and macular edema with exudates (dashed arrows). The patient was admitted to the hospital to treat malignant hypertension aggressively. (Reproduced with permission from Usatine RP, Smith MA, Mayeaux EJ, Chumley HS: The Color Atlas and Synopsis of Family Medicine, 3rd ed. New York, NY: McGraw Hill; 2019. Photo contributor: Paul D. Comeau.)
A central retinal vein occlusion (CRVO) is typically caused by a thrombotic event within the central retinal vein posterior to the lamina cribrosa. This is the location where the retinal nerve fiber layer exits the eye and becomes the myelinated optic nerve. Patients will present with a sudden change in vision, and examination will reveal dilation and tortuosity of the retinal veins, extensive retinal hemorrhages in all 4 quadrants, disk edema, and/or macular edema. The retinal hemorrhages are often pathognomonic and are described as “blood-and-thunder” hemorrhages (Figure 37–23). Approximately two-thirds of patients avoid chronic widespread ischemia (nonischemic CRVO) and will typically have vision better than 20/200. The other one-third of patients will have extensive retinal ischemia (ischemic CRVO), which often carries a very poor visual prognosis. In addition, they are at high risk of neovascularization. Workup involves testing for hypertension, diabetes, glaucoma, hyperviscosity, and hypercoagulability, as well as other less common etiologies.
The amount of hemorrhage (“blood and thunder”) is the most striking feature in this patient with a central retinal vein occlusion. Also note the blurred disk margin, the dilation and tortuosity of the venules, and the cotton-wool spots. In addition, retinal edema is suggested by blurring of the retinal details. (Reproduced with permission from Knoop KJ, Stack LB, Storrow AB, et al: The Atlas of Emergency Medicine, 4th ed. New York, NY: McGraw Hill; 2016. Photo contributor: Department of Ophthalmology, Naval Medical Center, Portsmouth, VA.)
It is not uncommon for patients to present with temporary vision loss (typically <30 minutes) in 1 eye. This is known as amaurosis fugax or a transient visual obscuration. It is the ocular equivalent of a transient ischemic attack of the brain. Because the retina is a neurosensory organ, temporary loss of blood flow can cause loss of function, but as long as blood flow is restored in a reasonable time frame, vision loss is not permanent. Although amaurosis fugax can be due to a variety of etiologies, the most common is embolic occlusion of the central retinal artery or 1 of its branches. Emboli are commonly from the carotid artery but may originate in the heart, heart valves, or aorta. The most common types of emboli are cholesterol (Hollenhorst) plaques, platelet fibrin, and calcium. In IV drug users, the differential should include talc emboli as well. Dilated examination should be focused on looking for an embolus, typically at an arterial bifurcation point. If giant cell arteritis is suspected, sedimentation rate and C-reactive protein values should be determined. Otherwise, initial workup should include carotid Doppler and cardiac echocardiography to look for an embolic source. Other risk factors include vascular insufficiency and hypercoagulable states.
If the acute, painless vision loss lasts longer than 30 minutes, there is a higher likelihood that the patient has experienced a central retinal artery occlusion (CRAO). In these patients, the embolic event does not self-resolve or the occlusion may be from another cause, such as thrombosis, giant cell arteritis, hypercoagulable states (eg, use of oral contraceptives, antiphospholipid syndrome, polycythemia), or other rarer etiologies such as lupus, migraine, syphilis, sickle cell disease, or polyarteritis nodosa. Patients with a CRAO will often present with global hypoperfusion and ischemia of the retina, giving it an edematous, opaque appearance. Because the fovea is thinner, the retina maintains a reddish transparency centrally; thus, a classic “cherry red spot” appearance can be seen (Figure 37–24). Vision loss is thought to become permanent after approximately 90 to 120 minutes of nonperfusion; therefore, attempts to reestablish blood flow by reducing the intraocular pressure are critical. This can be done by creating a paracentesis to release some aqueous fluid from the eye, instilling intraocular pressure-lowering medications, administering oral intraocular pressure-lowering medications, performing ocular massage, and/or administering carbon dioxide inhalation.
This central cherry red spot and peripheral cloudy swelling of the macula in a patient with central retinal artery occlusion was due to an embolus originating from a carotid artery atheromatous plaque. (Reproduced with permission from Kasper D, Fauci A, Hauser S, et al: Harrison’s Principles of Internal Medicine, 19th ed. New York, NY: McGraw Hill; 2015.)
In addition to causing embolic events, severe carotid artery stenosis can also cause global hypoperfusion of the entire eye. This is known as ocular ischemic syndrome. Patients may have a history of amaurosis fugax but often present with decreased vision and associated orbital or ocular pain. On dilated examination, these patients can have conjunctivitis, anterior cell uveitis, cataracts, optic nerve pallor, mid-peripheral retinal hemorrhages, and potentially neovascularization of the iris, angle, or posterior structures due to the global ischemia. Patients can have low intraocular pressure due to decreased ciliary body perfusion, but they may also have elevated pressure if there is evidence of angle neovascularization (ie, neovascular glaucoma). The physical exam should include carotid artery auscultation to evaluate for presence of a bruit. Treatment often requires a coordinated team effort, with the eye care specialist treating the neovascularization and glaucoma, if present, while the primary care team controls the systemic risk factors (hypertension, diabetes, and cholesterol). If occlusion of the carotid artery is significant, carotid endarterectomy is often considered.
In addition to vascular retinopathies, there are additional retinal pathologies that pose serious threats to vision. Age-related macular degeneration (AMD) is another leading cause of blindness in the United States. The primary risk factors for AMD are family history, age, female gender, white race, lightly colored irises, smoking, hypertension, ultraviolet exposure, and hyperopia. There are 2 forms of the disease. Approximately 90% of patients have the “dry” nonexudative form. In its early stages, dry AMD consists of pigmentation changes at the level of the RPE and presence of drusen. Drusen are excrescences of fatty lipid between the RPE and the Bruch membrane. On ophthalmic examination, drusen appear as small whitish-yellow deposits within the macula. As dry AMD progresses, the drusen become larger and more numerous. In addition, the RPE continues to change, and overlying photoreceptors begin to die off, creating geographic atrophy. Once photoreceptors have become damaged, they can no longer function properly, and the resulting scotomas are typically permanent. Once drusen reach a certain size, the use of a vitamin formulation containing vitamin C, vitamin E, β-carotene, zinc, and copper (ie, an Age-Related Eye Disease Study formula) has been shown to slow the progression of the dry form of the disease.
The other 10% of AMD patients have the “wet” exudative form of the disease. Wet AMD is characterized by the development of choroidal neovascularization that breaks through the Bruch membrane. The new blood vessels can cause detachment of the RPE from the Bruch membrane. In addition, the blood vessels can become leaky or bleed. The leaky blood vessels can cause folding or elevation of the retina. Thus, straight objects may look bent or distorted. If the blood vessels bleed, patients are at risk of developing scar tissue with large central scotomas. Patients can watch for AMD progression at home by using an Amsler grid to detect any early distortions in vision. In addition, regular dilated funduscopic examinations and occasional fluorescein angiography and optical coherence tomography testing may be used to detect abnormal blood vessels and leakage as well as retinal morphologic changes. Although there are few available treatments for the dry form of AMD, the discovery of anti-VEGF therapy has revolutionized the treatment of wet AMD. The anti-VEGF medications are given via monthly intraocular injection. These medications work by shrinking choroidal neovascularization. For the first time, instead of a slow decline in vision, some patients with wet AMD are now able to maintain or even improve vision.
Retinitis pigmentosa (RP) is not a single disease, but instead a family of genetic disorders that cause a progressive rod-cone dystrophy. The inheritance pattern can be autosomal recessive (most common), autosomal dominant (least severe), X linked (rarest but most severe), or sporadic. The disease primarily affects the production of proteins within the photoreceptors, eventually causing them to die. The disease can eventually cause loss of the photoreceptor layer and the outer nuclear layer of the retina as well. The RPE migrates inward and will surround some of the retinal vascular structures in the area of pathology. This leads to the classic “bone spicule” pattern seen in the peripheral retina (Figure 37–25). In addition, patients are noted to have a waxy pallor of the optic nerve and increased choroidal visibility due to RPE migration and outer retinal thinning. The initial symptoms noted by patients are difficulty seeing at night (ie, night blindness) and peripheral vision loss. Patients eventually progress to having color vision deficits as well as decreases in central visual acuity. Electroretinography testing classically shows decreased scotopic a- and b-wave amplitudes early in the disease. In later stages, electroretinography is flat with no response. RP can be seen in isolation or as part of a syndrome with associated systemic findings. Usher syndrome has an autosomal recessive inheritance and is associated with RP and deafness. Refsum disease is also autosomal recessive, and patients have a combination of RP symptoms and defects in fatty acid metabolism due to a deficiency of phytanic acid oxidase. Patients are instructed to avoid foods high in phytanic acid such as milk, animal fat, and leafy green vegetables. Bassen-Kornzweig syndrome is a combination of RP plus abetalipoproteinemia that is inherited in an autosomal recessive fashion. These patients can benefit from vitamin A and E treatment. Other conditions include chronic progressive external ophthalmoplegia and olivopontocerebellar atrophy.
This patient with retinitis pigmentosa demonstrates arteriolar narrowing and peripheral retinal pigment clumping (“bone spicules”). (Reproduced with permission from Riordan-Eva, P, Augsburger JJ: Vaughan & Asbury’s General Ophthalmology, 19th ed. New York, NY: McGraw Hill; 2018.)
The choroid, located between the retina and sclera, has a primary role of providing the outer retinal layers with oxygen and nutrients. It is comprised of a highly vascular plexus of interconnected vessels and is thought to have one of the highest blood flow rates of any tissue in the body. Typically, the vascular choroid, in conjunction with the RPE, provide the reddish-orange reflection seen when examining the eye. Although the posterior pole is typically a relatively uniform color and texture, benign choroidal nevi can occasionally be seen.
Choroidal nevi are a normal occurrence in the general population and are thought to have a prevalence of anywhere from 2% to 8%. Choroidal nevi are composed of melanocytes and typically have clearly defined borders. They are typically roundish and flat or minimally elevated. Although their size remains stable over time, development of overlying drusen or RPE changes may be seen (Figure 37–26). They should be documented by fundus photography and observed regularly for any evidence of change.
A. A typical melanocytic choroidal nevus is seen underlying the retinal blood vessels and is only about 0.25 mm thick by ultrasonography. B. This primary non–uniformly colored melanotic choroidal melanoma has a dome-shaped configuration. Note the central orangish pigment. On B-scan ultrasound, the lesion would have a low to medium internal reflectivity. (Reproduced with permission from Riordan-Eva, P, Augsburger JJ: Vaughan & Asbury’s General Ophthalmology, 19th ed. New York, NY: McGraw Hill; 2018.)
The primary differential diagnosis for a choroidal nevus is choroidal melanoma. Choroidal melanoma is the most common primary intraocular malignancy in the white population and is composed of malignant uveal melanocytes. Typically, on examination, the melanoma will have a brown/black dome or mushroom shape. There may be associated drusen, but more worrisome is the presence of orange pigmentation, subretinal fluid, or contiguous exudative retinal detachment (see Figure 37–26). B-scan ultrasound can be helpful in distinguishing nevi from melanomas. Worrisome features include thickness >2 mm, diameter >7 mm, and low to medium internal reflectivity. Ocular melanomas are treated by local plaque radiation, excision, or enucleation of the eye depending on the clinical and diagnostic findings.
Certain pathologies can affect both the retina and the underlying choroid simultaneously. Concurrent inflammation of both layers at the same time is known as chorioretinitis. There are many causes; however, probably the most common cause is toxoplasmosis infection. Typically, Toxoplasma gondii is a congenital infection that is passed from the mother to the baby during pregnancy. It is the most common cause of both pediatric uveitis and posterior uveitis. The life cycle of Toxoplasma includes oocysts, tachyzoites, and cyst bradyzoites. In humans, only the tachyzoites and cysts are seen. The tachyzoite is responsible for the inflammation and can be treated with antibiotics. However, the treatment does not affect the cysts; thus, infections may recur throughout the patient’s life. Steroids are used to target the inflammatory response. On examination, a pigmented chorioretinal scar can often be found in the macular region (Figure 37–27). Presence of an active vitreous cell with a white fuzzy border adjacent to the scar may indicate reactivation.
This chorioretinal scarring is due to old Toxoplasma chorioretinitis. The lesion is flat and pigmented. Areas of hypopigmentation are also present. (Reproduced with permission from Kasper D, Fauci A, Hauser S, et al: Harrison’s Principles of Internal Medicine, 19th ed. New York, NY: McGraw Hill; 2015.)
The optic nerve is composed of approximately 1.0 to 1.2 million retinal ganglion cell axons. The retinal ganglion cells are located in the inner retina (the ganglion cell layer), and their axons travel together in a coordinated fashion across the retina in the innermost retinal layer, the retinal nerve fiber layer. Once the axons reach the optic disk, they turn 90 degrees, pass through the lamina cribrosa, and exit the eye. Posterior to the lamina cribrosa, the axons become myelinated by oligodendrocytes and are packaged into bundles surrounded by astrocytes and microglia. The majority of axons terminate in the lateral geniculate nucleus. The optic nerve is composed of 4 major parts: the intraocular portion (1.0 to 1.5 mm), the intraorbital portion (30 to 40 mm), intracanalicular portion (5 to 8 mm), and the intracranial portion (10 mm). Damage at any of these locations can cause a profound impact on vision.
Glaucoma, a leading cause of blindness in the United States, comprises a group of diseases characterized by a chronic, progressive optic neuropathy (optic nerve atrophy) with corresponding visual field defects. Depending on whether or not gonioscopic examination reveals an open anterior chamber drainage angle with visible trabecular meshwork structures, the disease is classified as either open-angle or angle-closure glaucoma, respectively. Primary open-angle glaucoma is typically a bilateral but asymmetric disease, with individuals of African, Hispanic, and Asian descent appearing to be at a higher risk than whites. In addition, elevated intraocular pressure, advanced age, a first-degree family history of glaucoma, and a thin central cornea are some of the most commonly recognized risk factors. It should be noted that although a majority of patients with open-angle glaucoma have elevated intraocular pressure, approximately 30% of patients can have glaucomatous optic neuropathy and visual field defects while the intraocular pressure is within the normal range. For those with elevated intraocular pressure and an open drainage angle, the disease is thought to be related to an increased resistance to outflow of aqueous humor through the trabecular meshwork. There is some evidence of a genetic basis for the disease, with changes in the myocilin (MYOC) gene being some of the first genetic findings associated with the clinical diagnosis of glaucoma. However, the inheritance pattern appears to be quite complex, with a combination of genetic and possibly environmental factors.
Only during an acute angle closure attack, where intraocular pressure increases rapidly, do patients note a red, painful eye. Angle closure is typically caused by the iris pupillary margin making contact with the lens, causing pupillary block. This blockage of aqueous flow into the anterior chamber results in anterior bowing of the iris and acute obstruction of the outflow pathway with rapid elevation of intraocular pressure. Often in these cases, the patient may note “rainbow-colored halos” around lights due to the increased pressure causing corneal edema. Examination may reveal a mid-dilated pupil.
In open-angle glaucoma, the diagnosis is often made during a routine examination, and the patient will not have any visual complaints because the vision loss typically starts peripherally and slowly moves centrally. Not until late in the disease process is visual acuity lost. This is due to the pathophysiology of the disease. It is believed that axons are damaged as they pass through the lamina cribrosa. The axons at the superior and inferior poles appear to be at most risk. Due to the anatomic location of the retinal ganglion cells and axons, damage in these areas typically creates arcuate scotomas or nasal steps that respect the horizontal midline on visual field analysis. Optical coherence tomography of the retinal nerve fiber layer shows thinning. Examination of the nerve reveals an enlarged “cup-to-disk” ratio (Figure 37–28). This is a comparison of the diameters of the optic disk to the physiologic cup. The cup is the portion of the optic disk not occupied by axons. Thus, as the glaucomatous optic neuropathy progresses and the nerve becomes more atrophic, a smaller portion of the optic disk is occupied by axons and the cup-to-disk ratio increases. The only known treatment for glaucoma is the reduction of intraocular pressure, regardless of the type of disease. This is typically accomplished in 3 ways: use of topical or oral intraocular pressure-lowering medications (prostaglandin analogs, β-blockers, α-agonists, and carbonic anhydrase inhibitors), laser treatment of the trabecular meshwork, or conventional glaucoma surgery (typically a trabeculectomy or glaucoma shunt tube).
Glaucoma. A. An eye with a normal optic cup-to-disk ratio of 0.4 is seen. B. A patient with glaucoma has an increased optic cup-to-disk ratio of 0.8. (Part A, reproduced with permission from Usatine RP, Smith MA, Mayeaux EJ, Chumley HS: The Color Atlas and Synopsis of Family Medicine, 3rd ed. New York, NY: McGraw Hill; 2019. Photo contributor: Paul D. Comeau. B, reproduced with permission from Papadakis MA, McPhee SJ, Rabow MW: Current Medical Diagnosis & Treatment 2020. 59th ed. New York, NY: McGraw Hill; 2020.)
Just as increased intraocular pressure can cause damage to the optic nerve, so can increased intracranial pressure. Although the optic disk can become edematous as a result of other pathologies (eg, hypertensive emergency, inflammation, or infection), only edema caused by increased intracranial pressure is termed papilledema. The primary differential diagnosis for papilledema includes intracranial tumor, meningitis, and idiopathic intracranial hypertension (IIH; or pseudotumor cerebri). The first steps in narrowing down the diagnosis are to check the patient’s blood pressure and then obtain a magnetic resonance imaging (MRI) or CT scan of the brain to rule out malignancy. Once malignancies have been ruled out, a lumbar puncture with opening pressure should be obtained. IIH is much more common in females than males and is often first diagnosed in the fourth decade of life. Patients are typically overweight and present with headache, possible nausea and vomiting, and possible pulsatile tinnitus. On ophthalmic examination, the severity of the disk edema can be quite variable. Thus, the Frisen Papilledema Scale (grades 0 to 5) is used for grading the severity (Figure 37–29). Initially, the nasal aspect of the optic disk margin becomes blurred. The edema then spreads superior and inferior. Eventually as papilledema progresses, the entire disk margin becomes involved. Flame hemorrhages at the disk margin often present in advanced stages, and dilation and tortuosity of the vasculature are seen. Visual field testing often shows an enlarged blind spot, but arcuate defects similar to those seen in glaucoma patients can also be present. In addition, patients may have an inability to abduct the eye due to a cranial nerve VI palsy. This is due to a shift in the brainstem position at higher intracranial pressure, which causes tension on the sixth cranial nerve. The nerve can be damaged near the clivus as it enters the Dorello canal. Although a definitive cause for IIH is often difficult to identify, it is associated with several medications (tetracycline, nalidixic acid, isotretinoin, vitamin A, steroids, and oral contraceptive pills), dural sinus thrombosis, and pregnancy. Treatment is centered on reducing intracranial pressure through the use of oral medications (acetazolamide and furosemide) and reduction of weight (approximately 10% of body weight) when appropriate. If vision loss is severe, surgical intervention is often required. Optic nerve sheath fenestration and ventriculoperitoneal shunt are 2 of the most common surgeries used in the treatment of refractory IIH cases. Failure to relieve the intracranial pressure can lead to permanent vision loss and blindness.
The 6 images represent optic nerves with progressively worse papilledema based on the Frisen Papilledema Scale (grades 0 to 5). (Reproduced with permission from McKean SC, Ross JJ, Dressler DD, et al: Principles and Practice of Hospital Medicine, 2nd ed. New York, NY: McGraw Hill; 2017.)
Inflammation of the optic nerve, termed optic neuritis, is 1 of the most common optic neuropathies of early adulthood. Optic neuritis can be idiopathic, but it is often associated with multiple sclerosis, lupus, Lyme disease, sarcoidosis, syphilis, and other systemic diseases. Patients often present with a painful, unilateral loss of vision. Pain is typically exacerbated by eye movements. In addition, patients will likely have a relative afferent pupillary defect, decreased color vision (especially red desaturation), and visual field defects. Disk pallor may develop later in the disease process. Treatment for optic neuritis should include a consideration of IV steroids; however, oral steroids are contraindicated. The Optic Neuritis Treatment Trial has shown that approximately one-third of patients presenting with optic neuritis will go on to develop multiple sclerosis within 4 years. If the patient has had previous neurologic symptoms, the likelihood of multiple sclerosis is even higher.
The optic nerve and surrounding tissues are susceptible to tumor development as well. Optic nerve gliomas are common in children and have a high association with neurofibromatosis. Half of optic nerve gliomas remain intraorbital; however, half can also involve the intracranial portion of the optic nerve. When the intracranial portion is involved, there is always concern regarding extension to the hypothalamus due to the increased risk of mortality. Children often present with vision loss, strabismus, and optic disk edema and/or pallor. MRI is typically diagnostic. Optic nerve sheath meningiomas are also a concern. Typically, patients will present with decreased vision, an afferent pupillary defect, optic atrophy, and possibly retinochoroidal collateral shunt vessels coming off the optic nerve (Figure 37–30). Again, imaging is diagnostic, with calcification of the meninges showing up as a classic “railroad sign” along the length of the optic nerve.
This optic disk shows secondary optic atrophy with retinochoroidal collateral shunt vessels (arrows) due to an optic nerve sheath meningioma. (Reproduced with permission from Riordan-Eva, P, Augsburger JJ: Vaughan & Asbury’s General Ophthalmology, 19th ed. New York, NY: McGraw Hill; 2018.)
Although trauma can affect the eyelids and globe, it can also affect the optic nerve proper. Traumatic optic neuropathy can be caused by compression due to a retrobulbar hemorrhage. However, the intracanalicular portion can also be damaged if the canal is fractured. Patients typically present with decreased vision, visual field defects, and a relative afferent pupillary defect. CT of the head and orbits will show evidence of a fracture as well as hemorrhage. If hemorrhage is thought to be causing a significant problem, an urgent lateral canthotomy and cantholysis should be considered to decompress the orbit. For suspected traumatic optic neuropathy associated with optic canal fracture, use of high-dose steroids is common, although somewhat controversial.
Although a full discussion of pediatric eye problems is beyond the scope of this chapter, a few conditions deserve special mention.
The development of good visual acuity relies on the proper development of the central nervous system’s visual pathways and higher order visual processing centers after birth. Babies are actually born with poor visual acuity. Humans require the ability to obtain focused images on each retina for the final development of the central visual pathways, which allows perception of normal acuity. In addition, fixation with both eyes on the same target is required early in life for the development of stereoscopic vision (ie, depth perception). Without these early stimuli, children can develop amblyopia. If this is not recognized in time, it can lead to permanent visual loss.
Amblyopia is defined as abnormal visual acuity in an otherwise normal, healthy eye that cannot be corrected with glasses or contact lenses. There are multiple causes of amblyopia, including strabismic amblyopia, refractive amblyopia, and form deprivation amblyopia. Strabismus is an inability to fixate on a single object with both eyes at the same time due to a misalignment (Figure 37–31). If a preference develops for fixation out of 1 eye only, strabismic amblyopia can develop. The brain will ignore image information from the nonfixated eye in order to avoid diplopia. Refractive amblyopia is most commonly caused by a difference in refraction between the 2 eyes. One eye often has clearer vision; thus, it develops normally while information from the eye with the poorer image is ignored by the brain. Thus, the central pathways required for development of normal acuity do not fully develop. Finally, if the visual axis is blocked, preventing clear fixation on an object, form depravation amblyopia can develop. This can be caused by an eyelid covering the axis due to ptosis, corneal scaring, or cataract formation, to name a few.
This baby has congenital esotropia (strabismus). The corneal light reflex of the left eye appears more temporal than that of the right eye. Therefore, the left eye is deviated inward. (Reproduced with permission from Wilbur JK, Graber MA, Ray BE. Graber and Wilbur’s Family Medicine Examination & Board Review, 4th ed. New York, NY: McGraw Hill; 2017.)
Screening for congenital cataracts is critical in all children. As part of the newborn screening and well-child checkups, primary care physicians should examine the eyes of every child for lens opacification at every visit. This can be done quickly in the office. In a darkened room, most children’s eyes will dilate sufficiently without need of pharmacologic assistance. A light source such as a Finnoff transilluminator or penlight can be used to directly examine the lens. However, the best method is to use a direct ophthalmoscope at arm’s distance to evaluate the red reflex (Figure 37–32). The red reflex should be uniform without opacification. Any concern for congenital cataract should be referred to an ophthalmologist immediately because removal of amblyogenic cataracts is typically required by 3 months of age to avoid development of nystagmus and amblyopia.
A congenital cataract is seen in the right eye of this patient with dilated pupils. Note the normal, uniform red reflex in the left eye compared to the opacification of the red reflex in the right eye. (Reproduced with permission from Riordan-Eva, P, Augsburger JJ: Vaughan & Asbury’s General Ophthalmology, 19th ed. New York, NY: McGraw Hill; 2018.)
Fortunately, if caught early in childhood, amblyopia is treatable. Typically, treatment for amblyopia must occur before the age of 10 years. In many cases, after the age of 10 years, the central visual processing pathways are no longer plastic enough to develop the appropriate connections to obtain normal visual acuity. Treatment for amblyopia should only be done by qualified eye care specialists. Treatment involves first eliminating any barriers in the visual axis that might cause form deprivation, and then any refractive errors must be corrected. Next, treatments focus on forced use of the poorer seeing eye by patching, atropinizing (instilling atropine), or blurring the corrective lens of the good seeing eye for a portion of the day. This in turn forces the development of the central nervous system pathways from the poorer seeing eye. Strabismus realignment surgery is the final step once visual acuity has been maximized.
Nasolacrimal Duct Disorders
One of the first things parents often note and become concerned about is epiphora, or watery eyes. Children can be born with a congenital nasolacrimal duct obstruction that results in excessive tearing. Often the tear duct will open spontaneously but gentle massage over the nasolacrimal system is recommended as a method that can assist in opening the system. In a small percentage of cases, the tear duct will need to be probed manually to develop patency.
In addition to congenital obstruction of the nasolacrimal system, it can also be the site of infection. The nasolacrimal sac is an ideal location for bacterial growth in both the pediatric and adult population. Infection of the nasolacrimal sac, or dacrocystitis, is often caused by Staphylococcus, Streptococcus, Pseudomonas, and Haemophilus Influenza. Dacryocystitis often presents with conjunctival injection and an erythematous swelling just below the medial canthal tendon (Figure 37-33). Gentle pressure often causes reflux of purulent material from the punctum. Systemic antibiotics are required while warm compresses can promote drainage. The goal is to avoid chronic conjunctivitis and/or extension to orbital cellulitis due to a prolonged course. If spontaneous drainage does not occur, surgical incision and drainage may be necessary, however probing of the nasolacrimal system should not be undertaken during an acute infection.
This 10-year-old patient with streptococcal pharyngitis developed swelling and erythema over the medial lower lid and lacrimal sac, indicative of dacryocystitis. (Reproduced with permission from Knoop KJ, Stack LB, Storrow AB, et al: The Atlas of Emergency Medicine, 4th ed. New York, NY: McGraw Hill; 2016. Photo contributor: Kevin J. Knoop, MD, MS.)
The most common primary ocular tumor in children is retinoblastoma. It is critical that these tumors are diagnosed early as they are often fatal within 2 to 5 years of diagnosis if not treated. Retinoblastoma is a tumor developed from retinal progenitor cells within the eye during development. It is caused most often by a defect in the retinoblastoma tumor suppressor gene RB1. The congenital or hereditary form of retinoblastoma is a germline mutation that either occurs in utero or is passed down from the mother or father. These account for approximately one-third of the cases. Often in the congenital form of the disease, multiple tumors are seen within the eye and there is a higher chance of having bilateral involvement. “Trilateral” involvement is also possible with development of a pineoblastoma in the pineal gland. As these children grow into their late teens and early adulthood, they are also at a greater risk of developing other cancers, such as osteosarcoma (often the femur), soft tissue sarcomas, lymphoma, leukemia, melanoma, and others. Nonhereditary or sporadic retinoblastoma occurs in about two-thirds of the cases. These children do not have a germline mutation of the RB1 gene, and instead have acquired 2 mutations sporadically. Typically the sporadic variety is more likely to be in 1 eye only. More than half of all retinoblastoma tumors are diagnosed based on the finding of leukocoria either by the parents when taking a photograph or during routine examination (Figure 37-34). Another one-fourth are diagnosed due to the patient having developed strabismus. On dilated fundus examination, a whitish retinal mass will be seen. Patients may also have uveitis, neovascularization of the iris, hyphema, or angle closure glaucoma. An ultrasound of the eye will show a solid tumor with high internal reflectivity. CT or MRI scan of the head should be completed to rule out optic nerve and pineal gland involvement. On CT, calcification of the tumor may be seen as hyperintensities. Treatment depends on the size, number, and location of the tumors and can range from local photocoagulation or cryotherapy, to plaque radiation, to external beam radiation, to enucleation. For those in which tissue samples can be taken, the severity of pathology is determined by the level of differentiation. Rosettes are the hallmark pathology seen in the disease with Homer-Write rosettes, Flexner-Wintersteiner rosettes, and Fleurettes being seen at different levels of tumor differentiation. With proper treatment and follow-up, survival rate is now nearly 90% to 95%.
This patient with bilateral retinoblastomas has a white pupillary reflection (leukocoria) is seen in each eye. It is more pronounced in the right eye. Compare these reflexes to the normal red reflex seen in the left eye in Figure 37–32. (Reproduced with permission from Riordan-Eva, P, Augsburger JJ: Vaughan & Asbury’s General Ophthalmology, 19th ed. New York, NY: McGraw Hill; 2018.)
During fetal development, if the optic fissure does not close appropriately during the 6th-7th week of life, an ocular coloboma may develop. A coloboma is a hole or dysgenesis in part of the eye. Typically the optic fissure begins closing at the inferior portion of the eye near the equator and the closure then moves anterior and posterior. A coloboma most often involves the iris, ciliary body, choroid, retina, and/or optic nerve. An iris coloboma (anterior segment) will commonly present as a “keyhole” pupil extending inferiorly (Figure 37–35. Chorioretinal colobomas (posterior segment) often present with an inferonasal defect. Retinal detachment is a common complication that can be addressed with prophylactic laser cerclage.
Iris Coloboma. Iris coloboma is a congenital finding resulting from incomplete closure of the fetal ocular cleft. It appears as a teardrop pupil and may be mistaken for a sign of scleral rupture. (Reproduced with permission from Knoop KJ, Stack LB, Storrow AB, et al: The Atlas of Emergency Medicine, 4th ed. New York, NY: McGraw Hill; 2016. Photo contributor: R. Jason Thurman, MD.)
Several medications can have adverse ophthalmic side effects. Chief among those is the use of hydroxychloroquine for the treatment of chronic conditions such as lupus and rheumatoid arthritis. While the most common side effects are associated with nausea and mild gastroenteritis, the most concerning are the retinal toxicity effects. Patients at highest risk are those taking >6.5 mg/kg/day (typically >400 mg/day), patients with a cumulative lifetime dose of 1000 g, a duration of treatment longer than 5 years, those 60 years and older, individuals with concurrent retinal/macular disease, and patients with renal or hepatic dysfunction. The mechanism causing toxicity is not fully understood but hydroxychloroquine is known to bind to the retinal pigmented epithelial cells and thought to affect metabolism in other retinal cells. Most patients are asymptomatic early; however, a central or paracentral scotoma can be elicited by visual field and objective changes seen with fundus autofluorescence, retinal optical coherence tomography or multifocal electroretinogram. The classic “bullseye” maculopathy is typically seen later in the disease process. Patients should have annual visual fields and at least 1 objective test (usually OCT). If toxicity is observed, the prescribing physician should be informed and discontinuation discussed. Because of the accumulation in the RPE melanin cells, toxicity can progress for some time even after stopping the medication.
Ethambutol is another medication that can cause significant ophthalmic side effects. Ethambutol is a drug commonly used for the treatment of tuberculosis. The drug can cause a bilateral toxic optic neuropathy that is thought to be related to alterations in the cytosolic and mitochondrial calcium levels in retinal ganglion cells. It is thought that patients on 25 mg/kg/day are at the greatest risk, in addition to those with renal impairment which can cause accumulation of the drug. Most people recommend that patients with intact renal function be placed on doses in the 15 mg/kg/day range if possible to minimize the risk of complications.
Corticosteroids, primarily prednisolone, are drugs that is used as part of the standard post-operative care as well as for treatment of chronic inflammatory pathologies such as uveitis. The key adverse effects are the potential for increased intraocular pressure (steroid response glaucoma) and the development of cataracts (primarily posterior subcapsular cataracts). Some of these risks can be minimized by aggressive initial treatment followed by a tapering to a lower maintenance dosage. In addition, less potent corticosteroids can sometimes have less severe elevations of pressure. Therefore switching to fluoromethalone or loteprednol may be helpful.